Transdermal drug delivery system

Abstract

A multilaminate transdermal drug delivery system containing only dissolved drug in the drug reservoir is described. The delivery system comprises a backing layer, a reservoir layer and a membrane layer, wherein the drug in the reservoir is completely dissolved and the control of delivery is effected by the joint action of reservoir and membrane.

What is claimed is: 
     
       1. A transdermal drug delivery system for administering drug over an extended period comprising (a) a backing layer substantially impermeable to the drug and forming the top or outer surface of a bandage employing the delivery system,   (b) a reservoir layer comprising drug in a completely dissolved form in a continuous matrix or carrier,   (c) a membrane layer comprising a structure exhibiting some rate controlling property,   wherein a substantially constant release rate is achieved over a substantial part of the wear period by the combined action of the reservoir layer and the membrane layer wherein: ##EQU8##  are satisfied simultaneously, and wherein h is membrane thickness   K is partition coefficient between membrane and reservoir   D m  is diffusion coefficient of drug in membrane x max  is reservoir thickness     D r  is diffusion coefficient of drug in reservoir   T is the desired wear time of the bandage,   α is a design parameter ranging from but not including 0 to and including 0.67, and representing the fractional drop in the theoretical flux from time zero to the end of the wear period T and   β is a design parameter ranging from but not including 0 to and including 1, which allows adjustments to shape of release profile, initial concentration, C o , fraction of total drug depleted from the reservoir, h and x max  ; and   ≧ signifies equal to or greater than.   
     
     
       2. A transdermal delivery system according to claim 1 wherein α is in the range of from and including 0.01 to and including 0.67. 
     
     
       3. A transdermal delivery system according to claim 1 wherein α is in the range of from and including 0.02 to and including 0.3. 
     
     
       4. A transdermal delivery system of claim 1 wherein the membrane layer is a semipermeable membrane. 
     
     
       5. A transdermal delivery system of claim 1 wherein the membrane layer is a primed microporous membrane and wherein ##EQU9## τ is the tortuosity of the diffusion path through the membrane h is membrane thickness E is the fractional porosity of the membrane   K' is the drug partition coefficient between material in the micropores and the reservoir material   D m'   is drug diffusion coefficient in the material in the micropores of the membrane   x max  is reservoir thickness   D r  is diffusion coefficient of drug in reservoir   α is a design parameter ranging from but not including 0 to and including 0.67, and representing the fractional drop in the theoretical flux from time zero to the end of the wear period   β is a design parameter ranging from but not including 0 to and including 1, which allows adjustments to shape of release profile, initial concentration, C o , fraction or total drug depleted from the reservoir h and x max  ; and   ≧ signifies equal to or greater than.   
     
     
       6. A transdermal delivery system according to claim 5 wherein α ranges from and including 0.01 to and including 0.67. 
     
     
       7. A transdermal delivery system of claim 1 wherein the continuous matrix of the reservoir is solid. 
     
     
       8. A transdermal delivery system of claim 1 wherein the continuous matrix of the reservoir is a gel contained in a walled-container. 
     
     
       9. A transdermal delivery system comprising a system in accordance with claim 1 in which β is 1.0. 
     
     
       10. A transdermal delivery system comprising a system in accordance with claim 5 in which β is 1.0. 
     
     
       11. A transdermal delivery system comprising a system in accordance with claim 1 in which β ranges from but not including 0 to but not including 1. 
     
     
       12. A transdermal delivery system comprising a system in accordance with claim 5 in which β ranges from but not including 0 to but not including 1. 
     
     
       13. A transdermal delivery system according to claim 1 wherein the drug in the reservoir layer is timolol.